Decellularized Liver Matrix as Substrates for Hepatocyte Rescue in Acute Liver Toxicity
| Autor: | Kuang-Min Lee, 李光閔 |
|---|---|
| Rok vydání: | 2018 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 106 More and more scholars believe that the pathological changes of cirrhosis are a series of gradual clinical stages rather than a single disease. In the beginning, chronic hepatitis can lead to hepatocyte necrosis, and then if it is not controlled in time, it will evolve into liver fibrosis, which eventually causes the liver to become hard and form liver cirrhosis. However, such a cirrhosis process is irreversible, and the current treatment can only stop or slow down the damage of the liver. In addition, cirrhosis has long been one of the common causes of death in the adult population of the world, so the treatment of cirrhosis has been studied in the field of biomedicine. The previous study shows that the decellularized liver matrix-film can promote the recovery of D-galactosamine-induced injured hepatocytes. Therefore, in this study, we proposed a novel hypothesis that the injection of liver extracellular matrix into the fibrotic liver via the hepatic portal vein, may be an effective treatment for patients with cirrhosis. First, we developed a three-dimensional porous biomaterial by mixing liver extracellular matrix (LECM) and gelatin-hydroxyphenylpropionic acid (Glt-HPA). Then we cultured injured hepatocytes (Treated by GaIN, CHCl3, CCl4, repesctively) in the above-mentioned biomaterials with LECM-containing medium, the viability and functionality of injured hepatocytes was determined thereafter. In the result: (1) After 3 days culture of primary rat hepatocytes in Glt-HPA:LECM = 4:6, the secretion of albumin was about 50% and 20% higher than that in Glt-HPA:LECM = 5:5 and Glt-HPA (without LECM), separately; (2) After 5 days culture, the albumin secretion of the D-galactosamin-induced injury of hepatocytes in Glt-HPA-LECM (4:6) with the LECM-containing medium cultures was 2 times superior to that in Glt-HPA without the LECM-containing medium cultures (Negative). Also, the lactate dehydrogenase (LDH) activity of the GaIN-induced injury of hepatocytes in Glt-HPA-LECM (4:6) with the LECM-containing medium cultures was reduced to be similar to the non-injured hepatocytes in Glt-HPA with normal medium cultures (Blank). (3) After 5 days culture, the albumin secretion of the CHCl3-induced injury of hepatocytes in Glt-HPA-LECM (4:6) with the LECM-containing medium cultures was 1 time superior to Negative condition. Also, the LDH activity of the GaIN-induced injury of hepatocytes in Glt-HPA-LECM (4:6) with the LECM-containing medium cultures was reduced to be lower than Blank. (4) After 5 days culture, the albumin secretion of the CCl4-induced injury of hepatocytes in Glt-HPA-LECM (4:6) with the LECM-containing medium cultures was 12 % superior to Negative condition. Also, the LDH activity of the GaIN-induced injury of hepatocytes in Glt-HPA-LECM (4:6) with the LECM-containing medium cultures was reduced to be similar to Blank. In summary, Glt-HPA-LECM as a three-dimensional porous substrate showed high potential in increasing cell viability and albumin secretion of the primary hepatocyte. Furthermore, the LECM-containing medium did have the effect of restoring the activity of damaged hepatocytes and delaying the toxicity. Such results are believed to be of great significance for the future treatment of clinical cirrhosis and liver tissue engineering. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
| Externí odkaz: |
|